Differential localization of mammalian Lin-7 (MALS/Veli) PDZ proteins in the kidney

Am J Physiol Renal Physiol. 2005 Feb;288(2):F345-52. doi: 10.1152/ajprenal.00235.2004. Epub 2004 Oct 19.

Abstract

Lin-7 PDZ proteins, also called MALS or Velis, have been shown to coordinate basolateral membrane expression of various target proteins in renal epithelial cell models. Three different Lin-7/MALS/Veli isoforms, encoded by separate genes, have been identified. Here, we show that each Lin-7/MALS/Veli isoform is expressed in the kidney. Using MALS isoform-specific antibodies in combination with cell-specific marker antibodies, we found the products of the three mammalian Lin-7/MALS/Veli genes are differentially expressed along the length of the nephron. MALS/Veli 1 is predominately expressed in the glomerulus, thick ascending limb of Henle's loop (TAL), and the distal convoluted tubule (DCT). MALS/Veli 2 is exclusively expressed in the vasa recta. MALS/Veli 3 is largely located in the DCT and collecting duct. The subcellular localization of MALS/Veli proteins can vary, depending on the isoform and the cell type. In contrast to the predominate basolateral location of MALS/Veli 1 in the TAL and DCT and MALS/Veli 3 in the DCT, MALS/Veli 1 is found diffusely throughout the cytosol of intercalated cells. In the collecting duct, MALS/Veli 3 is chiefly located on the basal membrane. Collectively, these results suggest that different MALS/Veli isoforms may carry out cell type-specific functions. The TAL and distal segments appear to have the most significant capacity for a basolateral membrane-targeting mechanism involving different MALS/Veli isoforms.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Fluorescent Antibody Technique
  • Kidney Tubules, Collecting / physiology*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / chemistry
  • Membrane Proteins / pharmacology
  • Mice
  • Nephrons / physiology
  • Protein Isoforms
  • Rats
  • Rats, Sprague-Dawley
  • Vesicular Transport Proteins

Substances

  • Antibodies, Monoclonal
  • LIN7A protein, human
  • Membrane Proteins
  • Protein Isoforms
  • Vesicular Transport Proteins